Can Older Cells Solve Cloning's Problems?

If there is one thing that people on both sides of the cloning debate agree upon, it's that cloning is an incredibly inefficient process. When it comes to cloning animals, like Dolly and Snuppy, the process produces a healthy animal only a dismal 1% to 5% of the time. This hit-or-miss dilemma wouldn't matter much if producing identical animals were its only application, but cloning is also the foundation for one of the more promising ways that stem cells might be used to treat human disease with a patient's own cells. At this rate, even cloning's most ardent supporters agree that such a method won't be very reliable, or very realistic. If therapeutic cloning, as it is known, is to become a viable treatment option, then the first thing scientists need to do is boost the cloning technique's efficiency.

Researchers at University of Connecticut may have done just that. A report released in Nature Genetics Sunday by Xiangzhong Yang and Tao Cheng showed that by using a specific type of fully mature adult cell, they could improve the chances that they would produce a cloned embryo. Yang's team relied on the same technique that was used to create both Dolly and Snuppy, but instead of starting with cells that are still capable of dividing  like the mammary cell that created Dolly and the skin cell that became Snuppy  they used blood cells near the end of their life cycles that could no longer divide. It was these older, mature cells that produced more cloned embryos than the younger ones. "To our surprise, the fully differentiated cells were more efficient in producing cloned embryos," says Yang, a director of the University's Center for Regenerative Biology.

In fact, Yang's findings fly in the face of conventional wisdom in the cloning field, which held that cloning, which involves turning back the clock on adult cells, worked better with younger, more "embryo"-like cells. The less that the cloning process has to undo, the theory goes, the more successful the technique will be. In fact, there was good evidence to support this theory: In previous studies embryonic stem cells, which can generate all of the body's cell types, produced clones ten times more efficiently than adult stem cells, which can develop into only a restricted number of cell types. And when scientists had tried to clone fully differentiated cells, they had very little luck.

The Connecticut group's report, however, found that fully differentiated cells could prove useful in cloning, although they're still not sure why. Nearly 40% of these more mature cells developed to the blastocyst stage, at which point stem cells can be extracted, while only 4% of the more actively dividing cells did so. "That is good news for therapeutic cloning," notes Yang. From his research, Yang believes that most of the problems that occur in cloning occur after the blastocyst stage, when the embryo begins to divide to re-create all the tissue types in a developing fetus. "Based on our studies, we believe that development of a cloned embryo to the blastocyst stage is fairly normal," he says. "So cloning for [treatment] purposes is no problem."

Even Yang admits, however, that his study isn't the last word on cloning. He and his colleagues are already at work expanding this first trial, and investigating other ways to boost cloning's efficiency.